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Evaluating the Effect of Specific T Cells on Type 1 Diabetes Risk and Treatment

As researchers delve more deeply into trying to understand the origins of type 1 diabetes (T1D), they become increasingly aware that there is not a single disease pathogenesis, but rather multiple paths that vary from person to person. While they know that T1D results from the immune system attacking and destroying insulin-producing beta cells in the pancreas, there may be several different factors that contribute to this risk.

A recent study examined a variety of T cells, T cell receptors, antigens, and autoantibodies that may play a role in the development of T1D. One common factor they found was that individuals with an elevated level of islet autoantibodies in the peripheral blood are at increased risk of developing T1D within their lifetime. Researchers also know that in addition to risk genes, human leukocyte antigen (HLA) genes and the autoantibody glutamic acid decarboxylase (GAD) could vary from person to person and impact the effectiveness of targeted therapies. Children who possess two or more islet autoantibodies have around an “85% chance of developing T1D within 15 years and nearly a 100% lifetime risk for disease development.”

However, the mere presence of islet autoantibodies does not demonstrate disease state, because it could be years before clinical T1D presentation. In its early stage (stage 1), while the autoantibodies are present, beta cell function remains normal. As risk for T1D advances (stage 2), metabolic abnormalities develop. Finally, with T1D onset (stage 3), there is both a presence of autoantibodies and loss of beta cell function in regard to blood glucose. The staging paradigm was derived from data from the United States’ Diabetes AutoImmunity Study in the Young (DAISY), Finland’s Type 1 Diabetes Prediction and Prevention Study (DIPP), and Germany’s BABYDIAB studies.

Given the similarities of mouse models and human models when it comes to diabetes, mouse models are often used to study disease risk, evaluate pathogenesis, and assess potential treatment options. Researchers have found that specific antigens and T cells affect pancreatic islets differently. Understanding these antigen subsets could be critical in determining effective clinical therapeutics for prevention and treatment.

Thanks to the Network for Pancreatic Organ Donors (nPOD), more than 150 cases have been collected from organ donors with T1D since 2007, as well as more than 150 from non-diabetic donors and dozens of donors with autoantibodies but no clinical diabetes. These tissue donations have provided researchers with islets, cells, and data from multiple facets of the ody that contribute to T1D risk.

Understanding tissue specific T cells, antigens, and autoantibodies may help identify biomarkers of disease activity which could improve targeted therapeutic interventions. Eventually, this may help reduce risk of T1D by creating early intervention strategies.

While not involved with this study, Diabetes Research Connection (DRC) is focused on advancing understanding of T1D and improving prevention, diagnosis, and treatment options as well as progress toward a cure. Early career scientists receive critical funding to pursue novel, peer-reviewed research projects regarding multiple aspects of T1D. Learn more by visiting http://diabetesresearchconnection.org.

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Could Peripheral T Helper Cells Be Linked to Type 1 Diabetes Risk?

Type 1 diabetes (T1D) is a complex disease. Researchers believe that both genetics and autoantibodies play a role in development of the disease. In individuals with T1D, the immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas. A new study has found that peripheral T helper cells may play a role in initiating this process.

The study showed that children with T1D, as well as those who were autoantibody-positive who developed the disease later on, both had an increase in the amount of peripheral T helper cells circulating in their blood. Researchers believe that much like follicular helper T cells, peripheral T helper cells may also be involved in activating B cells which target against proteins in pancreatic islet cells and contribute to the development of T1D.

The ability to identify children who are at increased risk for the disease due to genetics as well as the elevated presence of peripheral T helper cells may improve options for proactively monitoring and treating T1D. It could also support the development of new immunotherapies for the disease.

More research is necessary to better understand the role of this T-cell subset and how it impacts type 1 diabetes risk and development of the disease as well as how it could improve treatment or prevention options. Though not involved with this study, Diabetes Research Connection (DRC) follows the latest developments and advancements regarding type 1 diabetes understanding, treatment, and prevention.

DRC provides critical funding for early career scientists pursuing novel research studies related to the disease and hopes to one day find a cure. To learn more about current projects or how to help, visit http://diabetesresearchconnection.org.

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